Objective:To investigate the radiation field and dose selection of patients with isolated chest wall recurrence (ICWR) after modified radical mastectomy, and analyze the prognostic factors related to subsequent chest wall recurrence.Methods:Clinical data of 201 patients with ICWR after mastectomy admitted to the Fifth Medical Center, Chinese PLA General Hospital from 1998 to 2018 were retrospectively analyzed. None of the patients received postoperative adjuvant radiotherapy. After ICWR, 48 patients (73.6%) underwent surgery and 155 patients (77.1%) received radiotherapy. Kaplan-Meier method was used to calculate the post-recurrence progression-free survival (PFS) rates and the difference was compared by log-rank test. Multivariate analysis was performed using Cox regression model. Competing risk model was adopted to estimate the subsequent local recurrence (sLR) rates after ICWR and the difference was compared with Gray test. Multivariate analysis was conducted using F&G analysis. Results:With a median follow up of 92.8 months after ICWR, the 5-year PFS rate was 23.2%, and the 5-year sLR rate was 35.7%. Multivariate analysis showed that patients with surgery plus radiotherapy and recurrence interval o F>12 months had a lower sLR rate. Patients with recurrence interval o F>48 months, local plus systemic treatment and surgery plus radiotherapy had a higher PFS rate. Among the 155 patients who received chest wall radiotherapy after ICWR, total chest wall irradiation plus local boost could improve the 5-year PFS rate compared with total chest wall irradiation alone (34.0% vs. 15.4%, P=0.004). Chest wall radiation dose (≤60 Gy vs.>60 Gy) exerted no significant effect upon the sLR and PFS rates (both P>0.05). In the 53 patients without surgery, the 5-year PFS rates were 9.1% and 20.5%( P=0.061) with tumor bed dose ≤60 Gy and>60 Gy, respectively. Conclusions:Local radiotherapy is recommended for patients with ICWR after modified radical mastectomy of breast cancer, including total chest wall radiation plus local boost. The radiation dose for recurrence should be increased to 60 Gy, and it should be above 60 Gy for those who have not undergone surgical resection. In addition, patients with ICWR still have a high risk of sLR, and more effective treatments need to be explored.

Objective:To analyze the prognosis of patients with isolated regional recurrence (RR) after mastectomy, and evaluate the efficacy of radiotherapy and identify the optimal radiation target volumes.Methods:Clinical data of 144 patients with first isolated RR after mastectomy between 2001 and 2018 were retrospectively analyzed. All patients had not received post-mastectomy radiotherapy. The primary endpoints consisted of the subsequent locoregional recurrence (sLRR), distant metastasis (DM), progression-free survival (PFS) and overall survival (OS).Results:With a median follow-up of 82.5 months after RR, the 5-year sLRR, DM, PFS and OS rates for the entire group were 42.1%, 71.9%, 22.9% and 62.6%, respectively. Local plus systemic therapy was an independent favorable prognostic factor for sLRR ( P<0.001) and PFS ( P=0.013). The sLRR rate in the surgery plus radiotherapy group was the lowest ( P<0.001). Surgery plus radiotherapy significantly reduced the 5-year risk of recurrence within the initially involved nodal regions ( P<0.001). Patients with chest wall irradiation obtained the 5-year subsequent chest wall recurrence rate of 12.1% compared to 14.8%( P=0.873) for those without chest wall irradiation. The subsequent supraclavicular recurrence rate was lower in patients with prophylactic supraclavicular irradiation than that without prophylactic supraclavicular irradiation (9.9% vs. 23.8%, P=0.206). The incidence rates of initially uninvolved axillary and internal mammary nodal recurrence were below 10% regardless of prophylactic irradiation or not. Conclusions:Patients with RR alone have an optimistic 5-year OS in the contemporary era. Comprehensive locoregional treatment including surgery and radiotherapy combined with systemic therapy is recommended. The chest wall, axillary and internal mammary nodal prophylactic irradiation should not be routinely performed for all patients with RR. The value of supraclavicular prophylactic irradiation remains to be evaluated.

BACKGROUND AND PURPOSE:Optimal radiation target volumes for breast cancer patients with their first isolated chest wall recurrence (ICWR) after mastectomy are controversial. We aimed to analyze the regional failure patterns and to investigate the role of prophylactic regional nodal irradiation (RNI) for ICWR.MATERIALS AND METHODS:Altogether 205 patients with ICWR after mastectomy were retrospectively analyzed. Post-recurrence progression-free survival (PFS) and overall survival (OS) rates were calculated by Kaplan-Meier method and the differences were compared with Log-rank test. Competing risk model was used to estimate the subsequent regional recurrence (sRR) and locoregional recurrence (sLRR) rates, and the differences were compared with Gray test.RESULTS:The 5-year sRR rate was 25.2% with median follow-up of 88.6 months. Of the 52 patients with sRR, 30 (57.7%) recurred in the axilla, 29 (55.8%) in supraclavicular fossa (SC), and five (9.6%) in internal mammary nodes. Surgery plus radiotherapy was independently associated with better sLRR and PFS rates (p<0.001). The ICWR interval of ≤ 4 years was associated with unfavorable sRR (p=0.062), sLRR (p=0.014), PFS (p=0.001), and OS (p=0.005). Among the 157 patients who received radiotherapy after ICWR, chest wall plus RNI significantly improved PFS (p=0.004) and OS (p=0.021) compared with chest wall irradiation alone. In the 166 patients whose ICWR interval was ≤ 4 years, chest wall plus RNI provided the best PFS (p<0.001) and OS (p=0.022) compared with chest wall irradiation alone or no radiotherapy.CONCLUSION:Patients with ICWR have a high-risk of sRR in SC and axilla. Chest wall plus RNI is recommended.

目的 探讨晚期乳腺癌肝转移导致重度肝功能异常后的治疗选择和疗效.方法 回顾性分析2003年至2018年我团队收治的乳腺癌肝转移导致严重肝功能异常患者49例,观察临床疗效和治疗方式的选择.结果 49例患者中28例继续行抗肿瘤治疗,获PR 7例,SD 7例,PD 14例,总有效率(ORR)为25.0％,疾病控制率(DCR)为50.0％.重度肝功能异常后治疗组与未治疗组中位生存期分别为3.0个月和0.5个月(P<0.05).治疗组中初治为单药化疗(或联合靶向治疗)21例,联合化疗3例,3例患者接受内分泌治疗,1例接受曲妥珠单抗单药治疗.在化疗方案中,紫杉类6例,卡培他滨5例,吉西他滨5例,长春瑞滨3例,依托泊苷3例,曲妥珠单抗联合治疗9例,抗血管生成联合治疗5例.结论 乳腺癌肝转移导致重度肝功能异常的患者如果前期治疗不充分继续行解救治疗仍然可能有效,但是建议首选有效率高、肝毒性小的药物,且采取初始药物剂量酌情下调等个体化给药模式.

Jiannan Liu 1,2 Feiyan Ma Bing Sun Yang Cong Liang Xuan Qian Wang Shikai Wu 1Academy of Military Medical Sciences, Beijing 100039, People’s Republic of China; 2Department of Radiation Oncology, The Fifth Medical Center of Chinese PLA General Hospital (Former 307th Hospital of the PLA), Beijing 100071, People’s Republic of China; 3Baoding No.1 Central Hospital Affiliated with Chengde Medical College, Baoding City, Hebei Province 071000, People’s Republic of China Purpose: Various reports found a relationship between lymphocyte-related blood parameters (LRBP), including absolute lymphocyte counts (ALC), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) and prognosis of breast cancer. Most of the studies focused on LRBP pre-treatment. Seldom have studies focused on LRBP during radiotherapy. We intended to perform a retrospective cohort study on the prognostic value of LRBP at the time point of lowest ALC during radiotherapy for breast cancer. Patients and methods: A total of 158 female patients were included in radiotherapy group because of the strict limitation standards of complete routine blood test results at pretreatment and pre-operation, and at least once a week during radiotherapy. Besides 221 patients, including the 158 patients of radiotherapy group, were adopted in pre-treatment group and pre-operation group. Results: ALC and PLR at the time point of lowest ALC during radiotherapy are prognostic predictors of breast cancer, and lower ALC and higher PLR are independent significant predictors of poor DFS. Besides, lower ALC, higher NLR and higher PLR at both pretreatment and pre-operation were found to be independent variables for predicting poor DFS. Conclusion: LRBP at pre-treatment, pre-operation, and during radiotherapy may serve as predictors of outcomes of breast cancer.

Docetaxel is an important anti-microtubule agent used to treat a variety of solid tumors, including breast cancer; notably, docetaxel-containing regimens improve outcomes for patients in metastatic, adjuvant, and neoadjuvant settings. However, the effectiveness of docetaxel in clinical practice can be compromised by suboptimal management of side effects. Here, we report two cases of docetaxel-based chemotherapy regimens in patients who exhibited invasive ductal breast cancer and underwent two different clinical treatment approaches. A 58-year-old postmenopausal female received salvage treatment with 8 cycles of docetaxel (67 mg/m(2)), and a 74-year-old female received 1 cycle of docetaxel (100 mg/m(2)). The two patients exhibited considerable hearing loss two days later. Of note, both patients had no hearing loss symptoms prior to docetaxel. Thus, ototoxicity may be a side effect of docetaxel that should be considered during treatment.

Purpose Various reports found a relationship between lymphocyte-related blood parameters (LRBP), including absolute lymphocyte counts (ALC), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) and prognosis of breast cancer. Most of the studies focused on LRBP pre-treatment. Seldom have studies focused on LRBP during radiotherapy. We intended to perform a retrospective cohort study on the prognostic value of LRBP at the time point of lowest ALC during radiotherapy for breast cancer. Patients and methods A total of 158 female patients were included in radiotherapy group because of the strict limitation standards of complete routine blood test results at pre-treatment and pre-operation, and at least once a week during radiotherapy. Besides 221 patients, including the 158 patients of radiotherapy group, were adopted in pre-treatment group and pre-operation group. Results ALC and PLR at the time point of lowest ALC during radiotherapy are prognostic predictors of breast cancer, and lower ALC and higher PLR are independent significant predictors of poor DFS. Besides, lower ALC, higher NLR and higher PLR at both pre-treatment and pre-operation were found to be independent variables for predicting poor DFS. Conclusion LRBP at pre-treatment, pre-operation, and during radiotherapy may serve as predictors of outcomes of breast cancer.

BackgroundPrevious studies have documented a high incidence of toxicity in patients with ultra‐central non‐small cell lung cancer (UC‐NSCLC) treated with stereotactic body radiation therapy (SBRT). However, these studies mainly focused on early stage patients and included small sample populations. We reviewed the outcomes and toxicity of SBRT in patients with advanced stage UC‐NSCLC treated at our institution.MethodsFifty‐one consecutive patients with advanced UC‐NSCLC treated with SBRT using a regular regimen of 35 Gy administered in five fractions between December 2014 and August 2017 were reviewed. UC was defined as tumors abutting or overlapping the trachea or the proximal bronchial tree. We included locally advanced patients who were unfit or unwilling to receive conventional chemoradiotherapy and patients with metastatic or postoperative recurrent disease. Clinical outcomes, dosimetric parameters, and SBRT toxicity were analyzed.ResultsThe median age was 63 years (range: 35–82), and the median tumor diameter was 6.8 cm (range: 2.1–12.4). The overall median follow‐up duration was 17 months (25.5 months for surviving patients). The median local control was 17 months for stage III patients and 11 months for stage IV or recurrent patients. Grade 3 or higher toxicity was observed in 9.8% of patients: G3 radiation pneumonitis (5.9%) and possible treatment‐related death (3.9%).ConclusionSBRT with a moderate dose in 4–6 fractions is effective and tolerable for patients with advanced stage UC‐NSCLC. However, caution should be taken considering possible treatment‐related death. Further studies are warranted.

Aim: To analyze the efficacy and toxicity of stereotactic body radiotherapy (SBRT) versus intensity-modulated radiotherapy (IMRT) in stage III patients with ultra-central squamous non-small-cell lung cancer (sqNSCLC). Methods: Forty-four stage III patients with ultra-central sqNSCLC receiving SBRT (n = 15) or IMRT (n = 29) between December 2014 and August 2017 were reviewed. Results: At a median follow-up of 16.5 months, the 1-year local control rate of SBRT and IMRT was 60.8 and 37.5%, respectively (p = 0.23); the median overall survival was 17 versus 18 months (p = 0.48); ≥3 grade toxicity was 20 versus 24.1% (p = 0.83). Conclusion: SBRT is effective and patient friendly for stage III patients with ultra-central sqNSCLC. Toxicity might be tolerable with a moderate dose five to six fraction regimen. However, more prospective studies are warranted.

目的 贝伐珠单抗是首个抗血管生成的分子靶向药物,可以与多种化疗药物联合用于治疗复发转移性乳腺癌.本研究旨在观察多西他赛联合贝伐珠单抗多线解救治疗晚期复发转移性乳腺癌的疗效和不良反应.方法 回顾性分析2008-05-01-2018-05-01解放军307医院肿瘤中心放疗科收治的接受多西他赛联合贝伐珠单抗多线治疗复发转移性乳腺癌患者27例,观察临床疗效,记录不良反应,计算无进展生存期.结果 27例患者均可评价疗效和不良反应,其中部分缓解11例,疾病稳定15例,客观有效率为40.7％,疾病控制率为96.3％,中位无进展生存时间为4个月(95％CI:2.9～5.1个月).其中21例患者既往辅助或解救治疗阶段曾使用过紫杉类药物,再次应用紫杉类联合贝伐珠单抗有效率为38.1％,中位无进展生存时间为4个月(95％CI:3.1～4.9个月).白细胞减少及粒细胞减少是主要不良反应,3～4级白细胞减少发生率为55.6％,其中3例伴粒细胞减少性发热.消化道反应7例、口腔粘膜炎4例、乏力5例、脱发7例,均为1～2级.结论 多西他赛联合贝伐珠单抗治疗多线解救失败的晚期难治性乳腺癌具有一定疗效,在既往应用过紫杉类药物的患者中也有一定疗效,不良反应可耐受,值得临床进一步研究及应用.

Background: Programmed cell death protein 1 (PD-1), an immune checkpoint molecule, has recently been recognized as a predictive and prognostic biomarker in several malignant tumors, but its diagnostic value remains largely unknown. Aim: We aimed to investigate the differential diagnostic efficiency of PD-1 and other immune molecules, and propose a panel of immune molecules combined with cancer antigen 15-3 (CA15-3) to distinguish breast cancer (BC) from benign breast disease (BBD). Methods: Ninety-one eligible BC patients and 31 BBD patients were enrolled. Pretreatment peripheral blood was collected and tested for mRNA expression of PD-1, cytotoxic T lymphocyte antigen 4 (CTLA-4), forkhead box P3 (FOXP3), transforming growth factor beta (TGF-β), interleukin-10 (IL-10), IL-2 receptor alpha (IL-2Rα), and cluster of differentiation 28 (CD28) by quantitative real-time PCR. Results: The diagnostic areas under curve (AUCs) of PD-1, IL-2Rα, and IL-10 for BC-BBD discrimination were 0.764, 0.758, and 0.743, respectively. The diagnostic efficiencies of these 2 parameters in distinguishing early-stage or advanced BC from BBD were consistent with a role in BC-BBD discrimination. A panel of PD-1 + IL-10 + IL-2Rα + CA15-3 showed the highest AUC (0.862), with sensitivity of 0.933 and specificity of 0.724, for BC-BBD discrimination. In addition, for early-stage BC discrimination, this panel also had the highest AUC (0.811), with a sensitivity of 0.933 and specificity of 0.614, while for advanced BC discrimination, a panel of PD-1 + IL-10 + CA15-3 exhibited the highest AUC (0.896), with a sensitivity of 0.933 and specificity of 0.783. Conclusion: These data indicate that the panel containing PD-1, IL-2Rα, IL-10, and CA15-3 can effectively discriminate BC from BBD with a high efficiency. After further confirmation, it could be used to complement conventional imaging modalities, especially in discriminating early-stage BC from BBD.

Transforming growth factor- (TGF-), interleukin-10 (IL-10), and forkhead box P3 (Foxp3) have important roles in breast cancer development. Previous studies confirmed a correlation between these immune molecules and tumor characteristics, but their association with nutritional status in breast cancer is largely unknown. We aimed to investigate the association between body mass index (BMI), hemoglobin, total protein, albumin, globulin (GLB), albumin/GLB ratio (AGR), pre-albumin, prognostic nutritional index, and TGF-, IL-10, and Foxp3 mRNA expression in patients with breast cancer. Quantitative real-time PCR was used to detect the mRNA expression of TGF-, IL-10, and Foxp3 in the peripheral blood of 107 patients with breast cancer and 21 healthy controls. We found that TGF- mRNA levels were 2.6-fold, 3.2-fold, and 2.3-fold higher in patients with low BMI (<23), low AGR, and high GLB, respectively, than in their counterparts (P<0.05). In addition, IL-10 mRNA expression levels in patients with normal BMI (<23) were 2.8-fold and 3.5-fold higher than in those who were overweight (23 BMI <25) and obese (BMI25), respectively (P<0.05). In addition, TGF-, IL-10, and Foxp3 mRNA levels were significantly higher in patients with breast cancer than in healthy controls (P<0.05). In summary, our results suggest that nutritional status, especially BMI, may strongly affect systematic immune function in patients with breast cancer. (c) 2018 IUBMB Life, 70(3):237-245, 2018